Henoch-Schönlein Purpura (IgA Vasculitis)

Henoch-Schönlein Purpura (HSP), now formally called IgA Vasculitis (IgAV), is the most common systemic vasculitis of childhood. It is driven by IgA1-dominant immune complex deposition in the walls of small blood vessels throughout the body — producing the classic tetrad of palpable purpura on the lower extremities, arthritis, colicky abdominal pain, and kidney inflammation. Although it sounds alarming, the vast majority of children recover fully within weeks. The critical job is recognizing it promptly, managing pain and joint swelling, and monitoring the kidneys carefully for the minority who develop lasting renal disease.

Table of Contents

  1. Overview and Epidemiology
  2. Pathophysiology: IgA1 Immune Complexes
  3. The Classic Tetrad
  4. Triggers and Precipitating Infections
  5. Diagnosis: Clinical and Laboratory
  6. Renal Involvement and Prognosis
  7. Treatment and Management
  8. HSP in Adults vs. Children
  9. Key Research Papers
  10. Connections
  11. Featured Videos

Overview and Epidemiology

IgA Vasculitis affects approximately 10–20 per 100,000 children per year in the developed world, with a peak incidence between ages 3 and 15. Boys are affected slightly more often than girls (roughly 1.5:1). The condition is distinctly seasonal — case clusters peak in autumn and winter, mirroring the surge in upper respiratory infections that typically precede it by 1–3 weeks.

The disease was described by Johann Schönlein in 1837, who linked purpura with joint involvement, and later expanded by Eduard Henoch in 1874, who added the gastrointestinal and renal components. In 2012, the European League Against Rheumatism (EULAR) and Paediatric Rheumatology European Society (PRES) renamed it IgA Vasculitis to reflect its molecular mechanism rather than its eponymous history — but most clinicians and patients still call it HSP.

The good news: roughly 94% of affected children achieve complete remission. Recurrences occur in approximately 30–40% of cases, but these are generally milder than the initial episode and resolve without escalating treatment.

Pathophysiology: IgA1 Immune Complexes

The central defect in IgA Vasculitis is the overproduction of aberrantly glycosylated IgA1. Healthy IgA1 molecules carry sugar chains (O-glycans) that include galactose on their hinge region. In HSP patients, many of these IgA1 molecules are produced with a galactose-deficient hinge — they are called "Gd-IgA1." This structural abnormality makes Gd-IgA1 molecules sticky: they aggregate into immune complexes and are poorly cleared by the liver.

These circulating Gd-IgA1 immune complexes deposit in the walls of small blood vessels — including those of the skin, joints, gut, and kidney glomeruli. Once deposited, they activate complement (via the alternative and lectin pathways) and recruit neutrophils and macrophages, producing the leukocytoclastic vasculitis (vessel inflammation with white blood cell infiltration) that underlies every symptom of the disease.

In the kidney, IgA1 deposits accumulate in the mesangium — the support tissue of the glomerular tuft — causing the identical pathological lesion seen in adult IgA nephropathy (Berger's disease). This molecular connection explains why HSP renal disease and IgA nephropathy are considered spectrum diseases sharing the same IgA1 glycosylation defect, just presenting at different ages and with different extents of systemic involvement.

The Classic Tetrad

The diagnosis of HSP / IgA Vasculitis is clinical. Four hallmark features constitute the classic tetrad:

1. Palpable Purpura

The defining feature: crops of raised, non-blanching, red-to-purple spots — true palpable purpura — distributed predominantly on the lower extremities and buttocks. The gravity-dependent pattern is characteristic: gravity concentrates hydrostatic pressure in the dependent small vessels, driving immune complex deposition there preferentially. The extensor surfaces of the arms and the periarticular areas around the knees and ankles are also commonly involved. The face and trunk are usually spared. Crucially, the purpura are non-thrombocytopenic: the platelet count is normal or elevated. This distinguishes HSP from idiopathic thrombocytopenic purpura (ITP) and meningococcemia.

Lesions evolve through stages — beginning as urticarial wheals or erythematous macules, progressing to raised purpura, then browning as they age. New crops often appear over days to weeks, especially if the child is on their feet. Bed rest visibly reduces new lesion formation by reducing hydrostatic pressure.

2. Arthritis or Arthralgia

Joint involvement occurs in 60–80% of children with HSP. The large joints — knees and ankles — are predominantly affected in a migratory, oligoarticular pattern. Joint swelling and pain can be severe enough to limit walking, but it is periarticular rather than true synovitis in most cases, meaning the joint space is not destructively involved. Permanent joint damage does not occur. Arthritis often precedes the rash by 1–2 days in some patients, which can initially lead to diagnostic confusion.

3. Abdominal Pain

Gastrointestinal involvement occurs in 50–75% of children. Colicky, periumbilical or diffuse abdominal pain results from IgA-immune-complex vasculitis of the gut wall, causing submucosal edema and hemorrhage. Children may have nausea, vomiting, and bloody stools. GI bleeding is typically occult (positive stool guaiac), though overt rectal bleeding can occur. The most feared GI complication is intussusception — HSP-associated intussusception occurs at the small bowel (ileoileal), unlike the more common ileocolic intussusception in idiopathic cases, and is a lead-point intussusception driven by submucosal edema. Ultrasound is the preferred diagnostic tool; air or saline enema reduction may fail for small-bowel intussusception, requiring surgical intervention in some cases.

4. Renal Involvement

Kidney disease occurs in 40–50% of children, typically presenting 4–6 weeks after the rash onset — sometimes after the skin and joint disease has resolved. Manifestations range from microscopic hematuria (the most common, often transient) to frank nephritic or nephrotic syndrome. Renal biopsy shows mesangial IgA deposits on immunofluorescence — the hallmark of IgA nephropathy. Prognosis is generally favorable for children with isolated hematuria, but those with significant proteinuria, nephrotic range losses, or severe hypertension are at risk for progressive renal disease. Approximately 1–2% of children with HSP develop end-stage renal disease over long-term follow-up.

Triggers and Precipitating Infections

An identifiable upper respiratory tract infection precedes HSP by 1–3 weeks in roughly two-thirds of cases. The most commonly implicated pathogens include:

Vaccines, drugs (penicillin, ACE inhibitors, NSAIDs), and insect bites have been reported as triggers in individual cases. COVID-19 infection has been associated with HSP-like presentations, though the relationship to MIS-C (multisystem inflammatory syndrome in children) remains under investigation — MIS-C shares some clinical overlap but involves different immune pathways (IgG-dominant vs. IgA-dominant).

Diagnosis: Clinical and Laboratory

There is no single confirmatory laboratory test for HSP. The 2010 EULAR/PRES/PRINTO classification criteria require palpable purpura (mandatory) plus at least one of four supporting criteria:

  1. Diffuse abdominal pain (colicky, acute onset)
  2. Arthritis (acute; any joint) or arthralgia without joint destruction
  3. Renal involvement (proteinuria, hematuria, red blood cell casts)
  4. Leukocytoclastic vasculitis or proliferative glomerulonephritis with predominant IgA deposition on biopsy

In a child with the classic tetrad, the diagnosis is made clinically and biopsy is unnecessary. Skin biopsy — when performed — shows IgA immunofluorescence staining of small vessel walls, confirming the diagnosis.

Typical laboratory findings:

Imaging: Abdominal ultrasound if GI involvement is significant — to evaluate for intussusception, bowel wall thickening, and free fluid. Scrotal ultrasound if testicular pain is present (orchitis occurs in ~10–15% of boys with HSP; must be differentiated from testicular torsion).

Renal Involvement and Prognosis

Renal involvement is the principal determinant of long-term outcome in HSP. It is essential to monitor urine for hematuria and proteinuria at every visit during the acute phase and for at least 6 months after the rash resolves, because nephritis can appear weeks after all other symptoms have cleared.

Risk stratification:

Renal biopsy indications include: nephrotic-range proteinuria, rapidly rising creatinine, hypertension requiring treatment, or any suspected severe nephritis. Histology is classified by the ISKDC (International Study of Kidney Disease in Children) grading system: Grade I (minimal changes) through Grade VI (crescentic involvement >75%). High-grade lesions (IV–VI) receive aggressive immunosuppression.

Long-term renal monitoring is important even in apparently recovered patients. Studies following HSP children for 10–23 years show that 1–2% develop ESRD and approximately 20% of those with initial significant renal involvement have hypertension or reduced GFR at long-term follow-up. Pregnancy can unmask latent HSP nephropathy in women who appeared to recover fully as children.

Treatment and Management

Mild disease (purpura + arthralgia only):

Moderate-to-severe abdominal pain or arthritis:

Significant renal disease:

Recurrent HSP: Up to 40% of children have at least one recurrence. Recurrences are usually milder and managed with the same supportive approach. Identifying and treating an underlying streptococcal carrier state may reduce recurrence frequency.

HSP in Adults vs. Children

IgA Vasculitis in adults (roughly 10% of all HSP cases) follows a substantially more severe course than in children:

The reason for the age-dependent severity difference is incompletely understood but may relate to differences in IgA1 glycosylation capacity, pre-existing subclinical renal damage, or differences in complement activation efficiency between mature and developing immune systems.

Key Research Papers

  1. Ozen S et al., 2006 — EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides — Annals of the Rheumatic Diseases — PMID: 16988076 — Established the first consensus classification criteria for childhood vasculitides, including the original criteria for HSP that distinguish it from other purpuric conditions.
  2. Ozen S et al., 2010 — EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis — Annals of the Rheumatic Diseases — PMID: 20819968 — Updated 2010 classification criteria (the currently used standard); validated in a multicenter international cohort; palpable purpura as mandatory criterion with one additional feature required.
  3. Jennette JC et al., 2013 — 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides — Arthritis & Rheumatism — PMID: 22895681 — International consensus renaming HSP to "IgA Vasculitis (Henoch-Schönlein)" and formally linking it to IgA nephropathy as a spectrum disease.
  4. Weiss PF et al., 2007 — Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review — Pediatrics — PMID: 17671069 — Systematic review finding that while corticosteroids reduce abdominal pain duration and severity, evidence does not support their use to prevent nephritis in unselected HSP patients.
  5. Heineke MH et al., 2017 — Pathophysiology of IgA vasculitis (Henoch-Schönlein purpura): an update — Seminars in Immunopathology — PMID: 28028614 — Comprehensive review of the IgA1 galactose-deficiency mechanism, Gd-IgA1 immune complex formation, complement activation pathways, and how these drive multiorgan involvement.
  6. Trnka P, 2013 — Henoch-Schönlein purpura in children — Journal of Paediatrics and Child Health — PMID: 24134630 — Practical pediatric review covering clinical presentation, diagnosis, management, and monitoring protocols; widely cited for its straightforward evidence-based management summary.
  7. Meadow SR et al., 1972 — Schönlein-Henoch nephritis — Quarterly Journal of Medicine — PMID: 4644875 — Early landmark study defining the spectrum of renal manifestations in HSP and establishing that the severity of nephritis, not the rash or joint disease, determines long-term prognosis.
  8. Narchi H, 2005 — Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with normal or minimal urinary findings — Archives of Disease in Childhood — PMID: 15798997 — Meta-analysis of 12 studies (1133 children) demonstrating that children with only microscopic hematuria have <1% risk of long-term renal damage, supporting a risk-stratified follow-up strategy.
  9. Ronkainen J et al., 2002 — Henoch-Schönlein purpura — Lancet — PMID: 12917434 — Landmark Finnish follow-up study of 141 HSP children over 23 years: 1.8% developed ESRD, 79% had complete resolution; identified nephrotic-range proteinuria as the strongest predictor of poor renal outcome.
  10. Trapani S et al., 2005 — Henoch Schönlein Purpura in childhood — Seminars in Arthritis and Rheumatism — PMID: 15942912 — Retrospective cohort of 150 Italian children detailing frequency of each component of the tetrad, recurrence rates (~33%), and outcomes, with emphasis on the importance of serial urinalysis monitoring.
  11. Audemard-Verger A et al., 2017 — IgA vasculitis in adults: Disease spectrum and outcome in a French multicenter retrospective study of 164 adults — Medicine — PMID: 29145296 — Largest adult HSP cohort study; confirms substantially more severe renal involvement in adults (75% nephritis) and worse long-term renal outcomes compared to pediatric disease.
  12. Oni L & Sampath S, 2019 — Childhood IgA Vasculitis (Henoch Schönlein Purpura) — Advances and Knowledge Gaps — Frontiers in Pediatrics — PMID: 31001517 — Contemporary review highlighting unresolved questions in HSP management including corticosteroid use, the role of renin-angiotensin blockade for early nephropathy, and emerging insights from genomics of IgA1 glycosylation defects.

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Connections

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